Parkinsonism Differential Diagnosis

Arriving at a differential diagnosis for Parkinsonism can be challenging. Below is a reference sheet that may help  in your determination. Following thr drop-down menus is a full matrix with all information provided.

Key Clinical Features
Asymmetric onset of bradykinesia, rigidity, 
4-6 Hz resting tremor, gait changes.

Pearls
Clear & definite response to levodopa

Pathology/Etiology
Alpha-synuclein-pre-dominant intracellular aggregates (Lewy bodies) in neurons. Dopaminergic cell loss in SNc. Dopamine deficiency leads to overactivity of indirect pathway, Reduction of inhibitory direct pathway in basal ganglia.

Imaging
No characteristic changes on MRI. Abnormal DaT Scan.

Key Clinical Features
4-12 Hz, bilateral postural & kinetic tremor, variable head & laryngeal involvement.

Pearls
Familial in ~50% of cases.
Alcohol responsiveness is often mentioned, but in reality is variable. Propranolol & primidone first line meds.

Pathology/Etiology
Cause unknown, with cerebellothalamic circuit hyperactivity.

Imaging
No characteristic changes on MRI. Normal  DaT Scan.

Key Clinical Features
MSA-P: Prominent dysautonomia w/ parkinsonism dominating.
MSA-C: Prominent dysautonomia w/ cerebellar ataxia dominating.

Pearls
Variable response to levodopa & may be lost later. Stridor is common & laryngospasm can cause sudden death.

Pathology/Etiology
Argyrophilic glial cytoplasmic inclusions positive for alpha-synuclein.

Imaging
“Hot cross buns sign” w/ T2 hyperintensity forming a cross in the pons. 

Key Clinical Features
Axial rigidity, vertical supranuclear gaze palsy, poor levodopa response & early falls.

Pearls
Classic phenotype known as, “Richardson syndrome”, additional phenotypes exist.
Facial dystonia, “procerus sign”, disinhibition.

Pathology/Etiology
4-repeat tauopathy with hyperphosphoryl-ated, tau-containing globose neurofibrillary tangles.
Tufted astrocytes, predominantly in brainstem.

Imaging
“Hummingbird sign” on sagittal MR images formed from atrophied midbrain w/ preserved pontine volume.

Key Clinical Features
Dementia onset w/in one year of onset of parkinsonism; hallucinations, cognitive fluctuations, & sensitivity to neuroleptics.

Pearls
Dopamine receptor blocking medication may cause severe & sometimes irreversible worsening of parkinsonism.

Pathology/Etiology
Alpha-synuclein- predominant intracellular aggregates (Lewy bodies) in neurons.

Imaging
Abnormal DaT scan.

Key Clinical Features
Highly asymmetric onset of akinetic-rigid parkinsonism, myoclonus, dystonia, &  cortical deficits like apraxia.

Pearls
Least common atypical parkinsonian syndrome.
Alien limb syndrome may occur.

Pathology/Etiology
4-repeat tauopathy w/ neurofibrillary tangles, astrocytic plaques, neuronal inclusions, predominantly in cortex.
Ballooned & achromatic neurons are classic.

Imaging
Asymmetric frontoparietal cortical atrophy on MRI.
Abnormal DaT scan.

Key Clinical Features
Parkinsonism, asymmetric or symmetric, in context of dopamine receptor blocking agents: antipsychotics, metoclopramide, prochlorperazine, promethazine

Pearls
Onset usually within one month of med start.
Resolution may be delayed after med stopped.

Pathology/Etiology
Blockade of D2 receptors is the most common etiology.
VMAT2 inhibitors deplete dopamine & may also cause DIP.

Imaging
No MRI findings. Normal DaT scan.

Key Clinical Features
Onset immediately following stroke or step-wise progression, w/ predominantly lower body involvement. Early gait & balance problems

Pearls
“Lower body parkinsonism” & poor response to levodopa.
Often with multiple vascular risk factors.

Pathology/Etiology
Microvascular disease, stroke.

Imaging
MRI – microvascular changes in key area of basal ganglia.

Key Clinical Features
Gait impairment, urinary incontinence, dementia in sequence.
Gait is described as “magnetic”.

Pearls
3 Ws: “wet, wobbly, wacky”. External lumbar drainage procedure.
Best predictor of response to ventriculoperito-neal shunt (VPS).

Pathology/Etiology
Often no clear cause, with impaired CSF absorption suspected. Striatal dopaminergic dysfunction implicated in motor phenotypes of NPH.

Imaging
Enlarged ventricles. Transependymal flow. Modified Evans Index can be used.

Key Clinical Features
Varying symptoms. Changes to quality of tremor.

Pearls
Distractibility, suggestibility, entrainment on exam.

Pathology/Etiology
No structural changes associated. Think of it as a “software problem”.

Imaging
Normal MRI. Normal DaT Scan.

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